Dispense interface for an ejection device

ABSTRACT

The invention inter alia relates to a dispense interface for an ejection device. The dispense interface comprises at least two inlets, at least one outlet and a part having multiple portions; wherein the multiple portions are connected by living hinges such that the multiple portions are foldable towards each other; wherein the multiple portions are configured to form a fluid channel arrangement between functional surfaces of the multiple portions facing each other when the multiple portions are folded towards each other; wherein at least two functional surfaces of the functional surfaces are inclined to each other when the multiple portions are folded towards each other; and wherein the fluid channel arrangement is configured to provide fluid communication between the at least two inlets and the at least one outlet.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a U.S. National Phase Application pursuant to35 U.S.C. § 371 of International Application No. PCT/EP2013/060156 filedMay 16, 2013, which claims priority to European Patent Application No.12168366.8 filed May 16, 2012. The entire disclosure contents of theseapplications are herewith incorporated by reference into the presentapplication.

FIELD OF INVENTION

The present patent application relates to medical devices for deliveringat least two drug agents from separate reservoirs. Such drug agents maycomprise a first and a second medicament. The medical device includes adose setting mechanism for delivering the drug agents automatically ormanually by the user.

BACKGROUND

The medical device can be an injector, for example a hand-held injector,especially a pen-type injector, that is an injector of the kind thatprovides for administration by injection of medicinal products from oneor more multidose cartridges. In particular, the present inventionrelates to such injectors where a user may set the dose.

The drug agents may be contained in two or more multiple dosereservoirs, containers or packages, each containing independent (singledrug compound) or pre-mixed (co-formulated multiple drug compounds) drugagents.

Certain disease states require treatment using one or more differentmedicaments. Some drug compounds need to be delivered in a specificrelationship with each other in order to deliver the optimum therapeuticdose. The present patent application is of particular benefit wherecombination therapy is desirable, but not possible in a singleformulation for reasons such as, but not limited to, stability,compromised therapeutic performance and toxicology.

SUMMARY

For example, in some cases it may be beneficial to treat a diabetic witha long acting insulin (also may be referred to as the first or primarymedicament) along with a glucagon-like peptide-1 such as GLP-1 or GLP-1analog (also may be referred to as the second drug or secondarymedicament).

Accordingly, there exists a need to provide devices for the delivery oftwo or more medicaments in a single injection or delivery step that issimple for the user to perform without complicated physicalmanipulations of the drug delivery device. The proposed drug deliverydevice provides separate storage containers or cartridge retainers fortwo or more active drug agents. These active drug agents are thencombined and/or delivered to the patient during a single deliveryprocedure. These active agents may be administered together in acombined dose or alternatively, these active agents may be combined in asequential manner, one after the other.

The drug delivery device also allows for the opportunity of varying thequantity of the medicaments. For example, one fluid quantity can bevaried by changing the properties of the injection device (e.g., settinga user variable dose or changing the device's “fixed” dose). The secondmedicament quantity can be changed by manufacturing a variety ofsecondary drug containing packages with each variant containing adifferent volume and/or concentration of the second active agent.

The drug delivery device may have a single dispense interface. Thisinterface may be configured for fluid communication with a primaryreservoir and with a secondary reservoir of medicament containing atleast one drug agent. The drug dispense interface can be a type ofoutlet that allows the two or more medicaments to exit the system and bedelivered to the patient.

The combination of compounds from separate reservoirs can be deliveredto the body via a double-ended needle assembly. This provides acombination drug injection system that, from a user's perspective,achieves drug delivery in a manner that closely matches the currentlyavailable injection devices that use standard needle assemblies. Onepossible delivery procedure may involve the following steps:

1. Attach a dispense interface to a distal end of the electro-mechanicalinjection device. The dispense interface comprises a first and a secondproximal needle. The first and second needles pierce a first reservoircontaining a primary compound and a second reservoir containing asecondary compound, respectively.

2. Attach a dose dispenser, such as a double-ended needle assembly, to adistal end of the dispense interface. In this manner, a proximal end ofthe needle assembly is in fluidic communication with both the primarycompound and secondary compound.

3. Dial up/set a desired dose of the primary compound from the injectiondevice, for example, via a graphical user interface (GUI).

4. After the user sets the dose of the primary compound, themicro-processor controlled control unit may determine or compute a doseof the secondary compound and preferably may determine or compute thissecond dose based on a previously stored therapeutic dose profile. It isthis computed combination of medicaments that will then be injected bythe user. The therapeutic dose profile may be user selectable.Alternatively, the user can dial or set a desired dose of the secondarycompound.

5. Optionally, after the second dose has been set, the device may beplaced in an armed condition. The optional armed condition may beachieved by pressing and/or holding an “OK” or an “Arm” button on acontrol panel. The armed condition may be provided for a predefinedperiod of time during which the device can be used to dispense thecombined dose.

6. Then, the user will insert or apply the distal end of the dosedispenser (e.g. a double ended needle assembly) into the desiredinjection site. The dose of the combination of the primary compound andthe secondary compound (and potentially a third medicament) isadministered by activating an injection user interface (e.g. aninjection button).

Both medicaments may be delivered via one injection needle or dosedispenser and in one injection step. This offers a convenient benefit tothe user in terms of reduced user steps compared to administering twoseparate injections.

The invention inter-alia faces the technical problem of providing asimple dispense interface for an ejection device that is easy tomanufacture.

According to a first aspect of the invention, a dispense interface foran ejection device comprises at least two inlets, at least one outletand a part having multiple portions; wherein the multiple portions areconnected by living hinges such that the multiple portions are foldabletowards each other; wherein the multiple portions are configured to forma fluid channel arrangement between functional surfaces of the multipleportions facing each other when the multiple portions are folded towardseach other; wherein at least two functional surfaces of the functionalsurfaces are inclined to each other when the multiple portions arefolded towards each other; and wherein the fluid channel arrangement isconfigured to provide fluid communication between the at least twoinlets and the at least one outlet.

The ejection device may be a drug delivery device such as a medicaldevice configured to eject a drug agent (e.g. a dose of a medicament)such as an infusion device or an injection device, for instance aninsulin injection pen. Injection devices may be used either by medicalpersonnel or by patients themselves. As an example, type-1 and type-2diabetes may be treated by patients themselves by injection of insulindoses, for example once or several times per day. In particular, theejection device may be a medical device configured to deliver (e.g.eject) at least two drug agents from separate reservoirs.

Alternatively, the ejection device may for instance be configured todeliver (e.g. eject) a two-component adhesive from separate fluidreservoirs comprising a first component of the two-component adhesive(e.g. a binder) and a second component of the two-component adhesive(e.g. a hardener), respectively.

The dispense interface may be a disposable part attachable to theejection device (e.g. the medical device). In particular, the dispenseinterface may be a single-use part attachable to the ejection device.Each of the at least two inlets of the dispense interface may beconfigured to reside in fluid communication with one of at least twoseparate fluid reservoirs of the ejection device when the dispenseinterface is attached to the ejection device.

The ejection device and/or the dispense interface may preferably beportable (e.g. handheld) devices.

The fluid channel arrangement may provide a fluid connection betweeneach of the at least two inlets of the dispense interface and the atleast one outlet of the dispense interface. Also, the fluid channelarrangement may provide a fluid connection between the at least twoinlets of the dispense interface. For instance, the fluid channelarrangement is at least partially Y-like, T-like or Z-like shaped.

The fluid channel arrangement may comprise one or more connected fluidchannels. The diameter of the fluid channels may be between 0.01 mm and10 mm. In particular, the diameter of the fluid channels may be between0.1 mm and 1 mm, for instance about 0.3 mm. The ratio between the lengthof the fluid channel arrangement and the diameter of the fluid channels(length:diameter ratio) may be substantially large, for instance between10:1 and 1000:1. In particular, the length:diameter ratio may be between20:1 and 100:1, for instance about 33:1 or 66:1. The length of the fluidchannel arrangement may preferably describe the longest fluid path ofthe fluid channel arrangement.

Integrally formed parts having a fluid channel arrangement with asubstantially large ratio between the length of the fluid channelarrangement and the diameter of the fluid channels (length:diameterratio) cannot be simply manufactured, for instance by moulding such asinjection moulding. This is inter-alia due to the fact that the fluidchannel arrangement is difficult to access. Complex tooling is necessaryto manufacture such parts.

Since the fluid channel arrangement of the dispense interface of thefirst aspect of the invention is formed between functional surfaces ofthe multiple portions facing each other when the multiple portions arefolded towards each other, manufacturing thereof is simplified. Thefunctional surfaces of the multiple portions are easily accessible.

The part having the multiple portions may for instance be manufacturedby moulding such as injection moulding, for instance by use of anopen-and-shut tool without the need for complex tooling. By joiningcorresponding portions of the multiple portions after manufacturingthereof, it is thus possible to form a joined part having fluid channelswith a large length:diameter ratio and/or a complex geometry and/ortight tolerances. For instance, the multiple portions may comprise atleast two body portions and at least two cover portions. Each of thebody portions may correspond to one of the cover portions.

The fluid channel arrangement may at least substantially be arranged ina sectional plane of the dispense interface. In particular, thesectional plane may for instance be inclined to contact/mating areas ofthe functional surfaces of the multiple portions when the multipleportions are folded towards each other. For instance, the sectionalplane may be a vertical plane of the dispense interface and/or alongitudinal plane of the dispense interface. Preferably, the fluidchannel arrangement should be understood to be at least substantiallyarranged in a sectional plane of the dispense interface if at least apredominant portion of the fluid channel arrangement (e.g. more than50%, preferably more than 75%, and more preferably more than 90%) is cutby the sectional plane of the dispense interface.

Fluid channels of the fluid channel arrangement may only be formedbetween functional surfaces of the multiple portions, but not allsurfaces facing each other when the multiple portions are folded towardseach other may be functional surfaces.

As described above, the multiple portions may comprise at least two bodyportions and at least two cover portions. The fluid channels of thefluid channel arrangement may (only) be formed between functionalsurfaces of the body portions and functional surfaces of the coverportions facing each other when the multiple portions are folded towardseach other. Each of the multiple portions may only have one functionalsurface. In addition to the fluid channels of the fluid channelarrangement formed between the functional surfaces of the multipleportions facing each other when the multiple portions are folded towardseach other, the multiple portions may comprise further fluid channels.

At least two functional surfaces of the functional surfaces are inclinedto each other when the multiple portions are folded towards each other.For instance, the functional surface of a first body portion may beinclined to the functional surface of a second neighboring body portionwhen the multiple portions are folded towards each other. The first andthe second body portion may be connected by a living hinge spaced fromthe functional surfaces. This is inter-alia advantageous to provide adispense interface with a fluid channel arrangement with a complexgeometry (e.g. with inclined fluid channels).

A living hinge may be a flexure bearing connecting two portions of themultiple portions. In particular, the living hinges may be integrallyformed with the multiple portions. Accordingly, the living hinges may bemade from the same material as the multiple portions. For instance, aliving hinge may be formed by a defined pre-weakening of the part havingthe multiple portions. For instance, a living hinge may at leastpartially be formed by a thinned portion of the part having the multipleportions, a perforated portion thereof and/or a cut portion thereof. Thetype of defined pre-weakening may be selected depending on the materialand thickness of the part having the multiple portions.

A living hinge may be configured to allow the two portions of themultiple portions connected by the living hinge to bend along the lineof the hinge (i.e. the rotational axis of the living hinge) such thatthe two portions are foldable towards each other.

A living hinge may be arranged next to neighboring surfaces of themultiple portions facing each other when the multiple portions arefolded towards each other. For instance, the living hinge may provide aflexible connection between these neighboring surfaces. The living hingemay be arranged at an edge of these neighboring surfaces. For instance,the living hinge may extend along these edges (with or withoutinterruptions).

For instance, each of the living hinges may have a rotational axis thatis angled to the sectional plane at least substantially comprising thefluid channel arrangement. As described above, the sectional plane atleast substantially comprising the fluid channel arrangement may be alongitudinal plane and/or a vertical plane. Accordingly, the rotationalaxis may be transversely oriented.

The at least one outlet of the dispense interface may serve as a commonoutlet for separate fluid reservoirs of the ejection device. Asdescribed above, each of these separate fluid reservoirs may reside influid communication with one of the at least two inlets of the dispenseinterface when the dispense interface is attached to the ejectiondevice.

The at least two inlets of the dispense interface and/or the at leastone outlet of the dispense interface may be either arranged in one ormore of the multiple portions or between facing surfaces of the multipleportions. For instance, each of the at least two inlets of the dispenseinterface and/or the at least one outlet of the dispense interface maybe formed integrally with multiple portions. Alternatively, the at leasttwo inlets of the dispense interface and/or the at least one outlet ofthe dispense interface may be subsequently mounted on the multipleportions.

As described above, corresponding portions of the multiple portions maybe joining components of the dispense interface. For instance, thecorresponding portions of the multiple portions may be configured to bejoined by folding the multiple portions towards each other.

During assembly of the dispense interface, the multiple portions may befolded towards each other such that the facing surfaces of the multipleportions contact/mate each other at a contact/mating area, and themultiple portions may fixed in this folded position and/or fitted withfurther components.

Due to the arrangement of the living hinge, the multiple portions may bemanufactured in a single manufacturing step. Furthermore, the count andcomplexity of assembly parts of the dispense interface is reduced. Theinvention is therefore inter alia advantageous to allow a simplemanufacturing and/or assembly of a dispense interface. Also, it allowsprovision of a fluid channel arrangement with a complex geometry. Also,it allows a cost-effective manufacturing/assembly of a disposabledispense interface (e.g. a single-use dispense interface).

According to an exemplary embodiment of the dispense interface of thefirst aspect of the invention, each of the at least two inlets is formedfrom a fluid connector emptying into the fluid channel arrangement,wherein each of the fluid connectors is configured to establish areleasable fluid connection with a corresponding fluid connector of afluid reservoir of the ejection device when the dispense interface isattached to the ejection device.

Non-limiting examples of a fluid connector may be a piercing needle, apiercable septum and/or a (male/female) Luer-connector. Such a fluidconnector may be integrally formed with the multiple portions.Alternatively, such a fluid connector may at least partially be inserted(e.g. potted/over-moulded/mounted) into the multiple portions. Forinstance, such a fluid connector may at least partially bepotted/over-moulded when the multiple portions are injection moulded.For instance, such a fluid connector may at least partially beglued/mounted in a separate step after the multiple portions have beeninjection moulded.

According to an exemplary embodiment of the dispense interface of thefirst aspect of the invention, the at least one outlet is formed from afluid connector, wherein the fluid channel arrangement empties into thefluid connector, and wherein the fluid connector is configured toestablish a fluid connection with a corresponding fluid connector of a(e.g. ejection/injection) needle assembly, when the needle assembly isattached to the dispense interface. The needle assembly may have aninjection needle for penetrating the skin of a patient such as acannula.

As described above, non-limiting examples of a fluid connector may be apiercing needle, a piercable septum and/or a (male/female)Luer-connector. Such a fluid connector may be integrally formed with themultiple portions. Alternatively, such a fluid connector may at leastpartially be inserted (e.g. potted/over-moulded/mounted) into themultiple portions. For instance, such a fluid connector may at leastpartially be potted/over-moulded when the multiple portions areinjection moulded. For instance, such a fluid connector may at leastpartially be glued/mounted in a separate step after the multipleportions have been injection moulded.

The fluid connector forming the at least one outlet of the dispenseinterface, allows to exchange the needle assembly more often than thedispense interface. This is inter-alia advantageous if the needleassembly is a single-use device which has to be replaced after a singleejection and the dispense interface is a disposable part which can beused for more than one ejection.

According to an exemplary embodiment of the dispense interface of thefirst aspect of the invention, the at least one outlet is formed from aneedle, wherein the fluid channel arrangement empties into the needle.The needle may be an injection needle for penetrating the skin of apatient such as a cannula.

The needle may at least partially be inserted (e.g.potted/over-moulded/mounted) into the multiple portions. For instance,the needle may at least partially be potted/over-moulded when themultiple portions are injection moulded. For instance, the needle may atleast partially be glued/mounted in a separate step after the multipleportions have been injection moulded. For instance, the needle may be anintegral part of the dispense interface.

Since the at least one outlet is already formed from a needle, noattachment of a separate needle assembly is necessary. This embodimentthus inter-alia allows to reduce the overall complexity of the dispenseinterface and/or the ejection device. This is inter-alia advantageous ifthe dispense interface is a single use device which has to be replacedafter a single ejection.

According to an exemplary embodiment of the dispense interface of thefirst aspect of the invention, the dispense interface further comprisesa valve arrangement configured to control a fluid flow from the at leasttwo inlets to the at least one outlet via the fluid channel arrangement.The valve arrangement may comprise one or more valves, preferably one ormore non-return valves. Such a valve arrangement may preferably beconfigured to prevent cross contamination of fluids contained inseparate fluid reservoirs of the ejection device. A preferred valvearrangement may also be configured so as to prevent back flow.Non-limiting examples of such valves are a diaphragm/flap valve, ashuttling valve, a moulded duck bill valve, a flat spring valve and/or arotating flap valve.

The valve arrangement may for instance be integrally formed with themultiple portions. Alternatively, the valve arrangement may for instancebe manufactured separately from the multiple portions. The valvearrangement may be inserted (e.g. potted/over-moulded/mounted) into themultiple portions. For instance, the valve arrangement may at leastpartially be potted/over-moulded when the multiple portions areinjection moulded. For instance, the valve arrangement may at leastpartially be mounted in a separate step after the multiple portions havebeen injection moulded.

According to an exemplary embodiment of the dispense interface of thefirst aspect of the invention, the multiple portions are folded towardseach other. In particular, the multiple portions may be folded towardseach other such that facing surfaces of the multiple portionscontact/mate each other at a contact/mating area. In this foldedposition, the fluid channel arrangement is formed between the functionalsurfaces of the multiple portions.

In particular, the multiple portions may be fixed in this foldedposition by a mechanical connection and/or by a material connection. Inparticular, the facing surfaces of the multiple portions may at leastpartially be connected with each other (e.g. at a contact/mating area)by such a mechanical connection and/or by a material connection.

Non-limiting examples of a mechanical connection are a frictional fit, abolted connection, a rivet connection and/or a clamp connection. Forinstance, complimentary fastening means may be integrally formed withthe multiple portions which are configured to mechanically fix themultiple portions in this folded position. Non-limiting examples of amaterial connection are glueing, welding (e.g. friction welding,ultrasonic welding and/or laser welding) and/or vulcanizing.

According to an exemplary embodiment of the dispense interface of thefirst aspect of the invention, the multiple portions comprise at leasttwo body portions and at least two cover portions, wherein each fluidchannel of the fluid channel arrangement is formed between a functionalsurface of a body portion and a functional surface of a cover portionwhen the multiple portions are folded towards each other. The functionalsurface of the body portion and the functional surface of the coverportion may face (e.g. contact/mate) each other when the multipleportions are folded towards each other.

According to an exemplary embodiment of the dispense interface of thefirst aspect of the invention, in each of the functional surfaces of thebody portions one or more fluid grooves are arranged. Additionally, alsofluid grooves may be arranged in the functional surfaces of the coverportions.

The fluid grooves may be any indentations on the functional surfaces ofthe body portions (and on the cover portions) which permit the passingof fluid along the functional surfaces thereof. The functional surfacesof the cover portions (and of the body portions) may be configured to(laterally) seal the fluid grooves when the multiple portions are foldedtowards each other such that a tight fluid channel arrangement isformed.

According to an exemplary embodiment of the dispense interface of thefirst aspect of the invention, at least one living hinge of the livinghinges connecting two body portions of the at least two body portions isspaced from the functional surfaces of these two body portions.

According to an exemplary embodiment of the dispense interface of thefirst aspect of the invention, the part having the multiple portions isintegrally formed by injection moulding (e.g. so-called clam shellmoulding). For instance, the multiple portions are formed in a singlestep by injection moulding by use of an open-and-shut tool.

For instance, use of an open-and-shut tool reduces the need for fragilecore pins or split lines with a groove arrangement. This also allows forrelatively complex and tight tolerance geometry without complex tooling.The moulding of key assembly snap features on the same component, suchas an outer protrusion on a portion, may also helps reduce tolerancestack-ups and also tends to allow for smaller fluid grooves (e.g. needlewells) and therefore smaller ullage.

For instance, polymer materials may be used in injection moulding of themultiple portions. Polymer materials are typically biocompatible. Forinstance, COP (cyclo-olefin polymer) materials may be used in injectionmoulding of the multiple portions. COP materials have a highbiocompatibility. For instance, COP materials have little to noextractables and most COP materialy can undergo sterilization by gammaradiation, steam and/or ethylene oxide. Other materials such as PP(poly-propylene) or HDPE (high density poly-ethylene) or other lessexpensive materials may be used, too. Especially, a single use dispenseinterface may be made from such a material, as the contact time with themedicament is rather short (only the time from priming the device untilthe injection is completed).

The exemplary embodiment of the dispense interface of the first aspectof the invention thus allows a simple manufacturing of the part havingthe multiple portions. Furthermore, it allows manufacturing this partfrom a biocompatible material. Potential problems of materialcompatibility, absorption and cross contamination between the fluids(e.g. drugs) and the polymer material are overcome by the selection of abiocompatible material and/or—for a single use dispense interface—by ashort contact time.

According to a second aspect of the invention, a method formanufacturing a dispense interface of the first aspect of the inventioncomprises (e.g. injection) moulding a part having multiple portions,folding the multiple portions towards each other; and fixing themultiple portions in this folded position (e.g. by establishing amaterial connection and/or by establishing a mechanical connection).

According to a third aspect of the invention, a system comprises thedispense interface of the first aspect of the invention and an ejectiondevice, wherein the dispense interface is attached to the ejectiondevice. The system may further comprise a needle assembly, wherein theneedle assembly is attached to the dispense interface. The dispenseinterface may provide a fluid connection between at least two fluidreservoirs of the ejection device and the needle assembly. As describedabove, the ejection device may be a medical device configured to deliver(e.g. eject) a medicament.

According to a fourth aspect of the invention, a method for using thesystem of the third aspect of the invention comprises attaching adispense interface of the first aspect of the invention to an ejectiondevice having at least two fluid reservoirs, ejecting a fluid from atleast one of the reservoirs through the dispense interface and detachingthe dispense interface from the ejection device. The method mayfurthermore comprise attaching a needle assembly to the dispenseinterface, wherein the fluid is ejected from at least one of thereservoirs through the dispense interface out of the needle assembly.

Exemplary features/embodiments (exhibiting further features) of theinvention have been described above, which are understood to apply tothe various aspects of the invention. These single features/embodimentsare considered to be exemplary and non-limiting, and to be respectivelycombinable independently from other disclosed features of the variousaspects of the invention as described above. Nevertheless, theseexemplary features/embodiments shall also be considered to be disclosedin all possible combinations with each other and with the variousaspects of the invention as described above.

BRIEF DESCRIPTION OF THE DRAWINGS

These as well as other advantages of various aspects of the presentinvention will become apparent to those of ordinary skill in the art byreading the following detailed description, with appropriate referenceto the accompanying drawings, in which:

FIG. 1 illustrates a perspective view of a delivery device with an endcap of the device removed;

FIG. 2 illustrates a perspective view of the delivery device distal endshowing the cartridge;

FIG. 3 illustrates a perspective view of the delivery device illustratedin FIG. 1 or 2 with one cartridge retainer in an open position;

FIG. 4 illustrates a dispense interface and a dose dispenser that may beremovably mounted on a distal end of the delivery device illustrated inFIG. 1;

FIG. 5 illustrates the dispense interface and the dose dispenserillustrated in FIG. 4 mounted on a distal end of the delivery deviceillustrated in FIG. 1;

FIG. 6 illustrates one arrangement of a needle assembly that may bemounted on a distal end of the delivery device;

FIG. 7 illustrates a perspective view of the dispense interfaceillustrated in FIG. 4;

FIG. 8 illustrates another perspective view of the dispense interfaceillustrated in FIG. 4;

FIG. 9 illustrates a cross-sectional view of the dispense interfaceillustrated in FIG. 4;

FIG. 10 illustrates an exploded view of the dispense interfaceillustrated in FIG. 4;

FIG. 11 illustrates a cross-sectional view of the dispense interface andneedle assembly mounted onto a drug delivery device, such as the deviceillustrated in FIG. 1;

FIG. 12 illustrates a perspective view of an alternative embodiment of adispense interface;

FIG. 13 illustrates another perspective view of the alternativeembodiment of a dispense interface illustrated in FIG. 12;

FIG. 14a illustrates an alternative embodiment of a valve arrangement ofa dispense interface;

FIG. 14b illustrates another alternative embodiment of a valvearrangement of a dispense interface;

FIG. 14c illustrates another alternative embodiment of a valvearrangement of a dispense interface;

FIG. 14d illustrates another alternative embodiment of a valvearrangement of a dispense interface; and

FIG. 14e illustrates another alternative embodiment of a valvearrangement of a dispense interface.

DETAILED DESCRIPTION

The drug delivery device illustrated in FIG. 1 comprises a main body 14that extends from a proximal end 16 to a distal end 15. At the distalend 15, a removable end cap or cover 18 is provided. This end cap 18 andthe distal end 15 of the main body 14 work together to provide a snapfit or form fit connection so that once the cover 18 is slid onto thedistal end 15 of the main body 14, this frictional fit between the capand the main body outer surface 20 prevents the cover from inadvertentlyfalling off the main body.

The main body 14 contains a micro-processor control unit, anelectro-mechanical drive train, and at least two medicament reservoirs.When the end cap or cover 18 is removed from the device 10 (asillustrated in FIG. 1), a dispense interface 200 is mounted to thedistal end 15 of the main body 14, and a dose dispenser (e.g., a needleassembly) can be attached to the interface. The drug delivery device 10can be used to administer a computed dose of a second medicament(secondary drug compound) and a variable dose of a first medicament(primary drug compound) through a single needle assembly, such as adouble ended needle assembly.

The drive train may exert a pressure on the bung of each cartridge,respectively, in order to expel the doses of the first and secondmedicaments. For example, a piston rod may push the bung of a cartridgeforward a pre-determined amount for a single dose of medicament. Whenthe cartridge is empty, the piston rod is retracted completely insidethe main body 14, so that the empty cartridge can be removed and a newcartridge can be inserted.

A control panel region 60 is provided near the proximal end of the mainbody 14. Preferably, this control panel region 60 comprises a digitaldisplay 80 along with a plurality of human interface elements that canbe manipulated by a user to set and inject a combined dose. In thisarrangement, the control panel region comprises a first dose settingbutton 62, a second dose setting button 64 and a third button 66designated with the symbol “OK.” In addition, along the most proximalend of the main body, an injection button 74 is also provided (notvisible in the perspective view of FIG. 1). The user interface of thedrug delivery device may comprise additional buttons, such as a “menu”button, a “back” button, or a “light” button to switch on anillumination of the display.

The cartridge holder 40 can be removably attached to the main body 14and may contain at least two cartridge retainers 50 and 52. Eachretainer is configured so as to contain one medicament reservoir, suchas a glass cartridge. Preferably, each cartridge contains a differentmedicament.

In addition, at the distal end of the cartridge holder 40, the drugdelivery device illustrated in FIG. 1 includes a dispense interface 200.As will be described in relation to FIG. 4, in one arrangement, thisdispense interface 200 includes a main outer body 210 that is removablyattached to a distal end 42 of the cartridge housing 40. As can be seenin FIG. 1, a distal end 214 of the dispense interface 200 preferablycomprises a needle hub 216. This needle hub 216 may be configured so asto allow a dose dispenser, such as a conventional pen type injectionneedle assembly, to be removably mounted to the drug delivery device 10.

Once the device is turned on, the digital display 80 shown in FIG. 1illuminates and provides the user certain device information, preferablyinformation relating to the medicaments contained within the cartridgeholder 40. For example, the user is provided with certain informationrelating to both the primary medicament (Drug A) and the secondarymedicament (Drug B).

As shown in FIG. 3, the first and second cartridge retainers 50, 52 maybe hinged cartridge retainers. These hinged retainers allow user accessto the cartridges. FIG. 3 illustrates a perspective view of thecartridge holder 40 illustrated in FIG. 1 with the first hingedcartridge retainer 50 in an open position. FIG. 3 illustrates how a usermight access the first cartridge 90 by opening up the first retainer 50and thereby having access to the first cartridge 90.

As mentioned above when discussing FIG. 1, a dispense interface 200 canbe coupled to the distal end of the cartridge holder 40. FIG. 4illustrates a flat view of the dispense interface 200 unconnected to thedistal end of the cartridge holder 40. A dose dispenser or needleassembly 400 that may be used with the interface 200 is also illustratedand is provided in a protective outer cap 420.

In FIG. 5, the dispense interface 200 illustrated in FIG. 4 is showncoupled to the cartridge holder 40. The axial attachment means 48between the dispense interface 200 and the cartridge holder 40 can beany known axial attachment means to those skilled in the art, includingsnap locks, snap fits, snap rings, keyed slots, and combinations of suchconnections. The connection or attachment between the dispense interfaceand the cartridge holder may also contain additional features (notshown), such as connectors, stops, splines, ribs, grooves, pips, clipsand the like design features, that ensure that specific hubs areattachable only to matching drug delivery devices. Such additionalfeatures would prevent the insertion of a non-appropriate secondarycartridge to a non-matching injection device.

FIG. 5 also illustrates the needle assembly 400 and protective cover 420coupled to the distal end of the dispense interface 200 that may bescrewed onto the needle hub of the interface 200. FIG. 6 illustrates across sectional view of the double ended needle assembly 400 mounted onthe dispense interface 200 in FIG. 5.

The needle assembly 400 illustrated in FIG. 6 comprises a double endedneedle 406 and a hub 401. The double ended needle or cannula 406 isfixedly mounted in a needle hub 401. This needle hub 401 comprises acircular disk shaped element which has along its periphery acircumferential depending sleeve 403. Along an inner wall of this hubmember 401, a thread 404 is provided. This thread 404 allows the needlehub 401 to be screwed onto the dispense interface 200 which, in onepreferred arrangement, is provided with a corresponding outer threadalong a distal hub. At a center portion of the hub element 401 there isprovided a protrusion 402. This protrusion 402 projects from the hub inan opposite direction of the sleeve member. A double ended needle 406 ismounted centrally through the protrusion 402 and the needle hub 401.This double ended needle 406 is mounted such that a first or distalpiercing end 405 of the double ended needle forms an injecting part forpiercing an injection site (e.g., the skin of a user).

Similarly, a second or proximal piercing end 408 of the needle assembly400 protrudes from an opposite side of the circular disc so that it isconcentrically surrounded by the sleeve 403. In one needle assemblyarrangement, the second or proximal piercing end 408 may be shorter thanthe sleeve 403 so that this sleeve to some extent protects the pointedend of the back sleeve. The needle cover cap 420 illustrated in FIGS. 4and 5 provides a form fit around the outer surface of the hub 401.

Referring now to FIGS. 4 to 11, one preferred arrangement of thisinterface 200 will now be discussed. In this one preferred arrangement,this interface 200 comprises:

-   -   a. a main outer body 210,    -   b. an first inner body 220,    -   c. a second inner body 230,    -   d. a first piercing needle 240,    -   e. a second piercing needle 250,    -   f. a valve seal 260, and    -   g. a septum 270.

The main outer body 210 comprises a main body proximal end 212 and amain body distal end 214. At the proximal end 212 of the outer body 210,a connecting member is configured so as to allow the dispense interface200 to be attached to the distal end of the cartridge holder 40.Preferably, the connecting member is configured so as to allow thedispense interface 200 to be removably connected the cartridge holder40. In one preferred interface arrangement, the proximal end of theinterface 200 is configured with an upwardly extending wall 218 havingat least one recess. For example, as may be seen from FIG. 8, theupwardly extending wall 218 comprises at least a first recess 217 and asecond recess 219.

Preferably, the first and the second recesses 217, 219 are positionedwithin this main outer body wall so as to cooperate with an outwardlyprotruding member located near the distal end of the cartridge housing40 of the drug delivery device 10. For example, this outwardlyprotruding member 48 of the cartridge housing may be seen in FIGS. 4 and5. A second similar protruding member is provided on the opposite sideof the cartridge housing. As such, when the interface 200 is axiallyslid over the distal end of the cartridge housing 40, the outwardlyprotruding members will cooperate with the first and second recess 217,219 to form an interference fit, form fit, or snap lock. Alternatively,and as those of skill in the art will recognize, any other similarconnection mechanism that allows for the dispense interface and thecartridge housing 40 to be axially coupled could be used as well.

The main outer body 210 and the distal end of the cartridge holder 40act to form an axially engaging snap lock or snap fit arrangement thatcould be axially slid onto the distal end of the cartridge housing. Inone alternative arrangement, the dispense interface 200 may be providedwith a coding feature so as to prevent inadvertent dispense interfacecross use. That is, the inner body of the hub could be geometricallyconfigured so as to prevent an inadvertent cross use of one or moredispense interfaces.

A mounting hub is provided at a distal end of the main outer body 210 ofthe dispense interface 200. Such a mounting hub can be configured to bereleasably connected to a needle assembly. As just one example, thisconnecting means 216 may comprise an outer thread that engages an innerthread provided along an inner wall surface of a needle hub of a needleassembly, such as the needle assembly 400 illustrated in FIG. 6.Alternative releasable connectors may also be provided such as a snaplock, a snap lock released through threads, a bayonet lock, a form fit,or other similar connection arrangements.

The dispense interface 200 further comprises a first inner body 220.Certain details of this inner body are illustrated in FIG. 8-11.Preferably, this first inner body 220 is coupled to an inner surface 215of the extending wall 218 of the main outer body 210. More preferably,this first inner body 220 is coupled by way of a rib and groove form fitarrangement to an inner surface of the outer body 210. For example, ascan be seen from FIG. 9, the extending wall 218 of the main outer body210 is provided with a first rib 213 a and a second rib 213 b. Thisfirst rib 213 a is also illustrated in FIG. 10. These ribs 213 a and 213b are positioned along the inner surface 215 of the wall 218 of theouter body 210 and create a form fit or snap lock engagement withcooperating grooves 224 a and 224 b of the first inner body 220. In apreferred arrangement, these cooperating grooves 224 a and 224 b areprovided along an outer surface 222 of the first inner body 220.

In addition, as can be seen in FIG. 8-10, a proximal surface 226 nearthe proximal end of the first inner body 220 may be configured with atleast a first proximally positioned piercing needle 240 comprising aproximal piercing end portion 244. Similarly, the first inner body 220is configured with a second proximally positioned piercing needle 250comprising a proximally piercing end portion 254. Both the first andsecond needles 240, 250 are rigidly mounted on the proximal surface 226of the first inner body 220.

Preferably, this dispense interface 200 further comprises a valvearrangement. Such a valve arrangement could be constructed so as toprevent cross contamination of the first and second medicamentscontained in the first and second reservoirs, respectively. A preferredvalve arrangement may also be configured so as to prevent back flow andcross contamination of the first and second medicaments.

In one preferred system, dispense interface 200 includes a valvearrangement in the form of a valve seal 260. Such a valve seal 260 maybe provided within a cavity 231 defined by the second inner body 230, soas to form a holding chamber 280. Preferably, cavity 231 resides alongan upper surface of the second inner body 230. This valve seal comprisesan upper surface that defines both a first fluid groove 264 and secondfluid groove 266. For example, FIG. 9 illustrates the position of thevalve seal 260, seated between the first inner body 220 and the secondinner body 230. During an injection step, this seal valve 260 helps toprevent the primary medicament in the first pathway from migrating tothe secondary medicament in the second pathway, while also preventingthe secondary medicament in the second pathway from migrating to theprimary medicament in the first pathway. Preferably, this seal valve 260comprises a first non-return valve 262 and a second non-return valve268. As such, the first non-return valve 262 prevents fluid transferringalong the first fluid pathway 264, for example a groove in the sealvalve 260, from returning back into this pathway 264. Similarly, thesecond non-return valve 268 prevents fluid transferring along the secondfluid pathway 266 from returning back into this pathway 266.

Together, the first and second grooves 264, 266 converge towards thenon-return valves 262 and 268 respectively, to then provide for anoutput fluid path or a holding chamber 280. This holding chamber 280 isdefined by an inner chamber defined by a distal end of the second innerbody both the first and the second non return valves 262, 268 along witha pierceable septum 270. As illustrated, this pierceable septum 270 ispositioned between a distal end portion of the second inner body 230 andan inner surface defined by the needle hub of the main outer body 210.

The holding chamber 280 terminates at an outlet port of the interface200. This outlet port 290 is preferably centrally located in the needlehub of the interface 200 and assists in maintaining the pierceable seal270 in a stationary position. As such, when a double ended needleassembly is attached to the needle hub of the interface (such as thedouble ended needle illustrated in FIG. 6), the output fluid path allowsboth medicaments to be in fluid communication with the attached needleassembly.

The hub interface 200 further comprises a second inner body 230. As canbe seen from FIG. 9, this second inner body 230 has an upper surfacethat defines a recess, and the valve seal 260 is positioned within thisrecess. Therefore, when the interface 200 is assembled as shown in FIG.9, the second inner body 230 will be positioned between a distal end ofthe outer body 210 and the first inner body 220. Together, second innerbody 230 and the main outer body hold the septum 270 in place. Thedistal end of the inner body 230 may also form a cavity or holdingchamber that can be configured to be fluid communication with both thefirst groove 264 and the second groove 266 of the valve seal.

Axially sliding the main outer body 210 over the distal end of the drugdelivery device attaches the dispense interface 200 to the multi-usedevice. In this manner, a fluid communication may be created between thefirst needle 240 and the second needle 250 with the primary medicamentof the first cartridge and the secondary medicament of the secondcartridge, respectively.

FIG. 11 illustrates the dispense interface 200 after it has been mountedonto the distal end 42 of the cartridge holder 40 of the drug deliverydevice 10 illustrated in FIG. 1. A double ended needle 400 is alsomounted to the distal end of this interface. The cartridge holder 40 isillustrated as having a first cartridge containing a first medicamentand a second cartridge containing a second medicament.

When the interface 200 is first mounted over the distal end of thecartridge holder 40, the proximal piercing end 244 of the first piercingneedle 240 pierces the septum of the first cartridge 90 and therebyresides in fluid communication with the primary medicament 92 of thefirst cartridge 90. A distal end of the first piercing needle 240 willalso be in fluid communication with a first fluid path groove 264defined by the valve seal 260.

Similarly, the proximal piercing end 254 of the second piercing needle250 pierces the septum of the second cartridge 100 and thereby residesin fluid communication with the secondary medicament 102 of the secondcartridge 100. A distal end of this second piercing needle 250 will alsobe in fluid communication with a second fluid path groove 266 defined bythe valve seal 260.

FIG. 11 illustrates a preferred arrangement of such a dispense interface200 that is coupled to a distal end 15 of the main body 14 of drugdelivery device 10. Preferably, such a dispense interface 200 isremovably coupled to the cartridge holder 40 of the drug delivery device10.

As illustrated in FIG. 11, the dispense interface 200 is coupled to thedistal end of a cartridge housing 40. This cartridge holder 40 isillustrated as containing the first cartridge 90 containing the primarymedicament 92 and the second cartridge 100 containing the secondarymedicament 102. Once coupled to the cartridge housing 40, the dispenseinterface 200 essentially provides a mechanism for providing a fluidcommunication path from the first and second cartridges 90, 100 to thecommon holding chamber 280. This holding chamber 280 is illustrated asbeing in fluid communication with a dose dispenser. Here, asillustrated, this dose dispenser comprises the double ended needleassembly 400. As illustrated, the proximal end of the double endedneedle assembly is in fluid communication with the chamber 280.

In one preferred arrangement, the dispense interface is configured sothat it attaches to the main body in only one orientation, that is it isfitted only one way round. As such as illustrated in FIG. 11, once thedispense interface 200 is attached to the cartridge holder 40, theprimary needle 240 can only be used for fluid communication with theprimary medicament 92 of the first cartridge 90 and the interface 200would be prevented from being reattached to the holder 40 so that theprimary needle 240 could now be used for fluid communication with thesecondary medicament 102 of the second cartridge 100. Such a one wayaround connecting mechanism may help to reduce potential crosscontamination between the two medicaments 92 and 102.

FIGS. 12 to 13 illustrate an embodiment of a dispense interface 2000alternative to the embodiment of the dispense interface 200 illustratedin FIGS. 7 to 11. In FIGS. 12 to 13 the same reference signs as in FIGS.7 to 11 are used for parts which are similar. Furthermore, at thispoint, it is mainly referred to the above description of the embodimentof the dispense interface 200 illustrated in FIGS. 7 to 11 and,basically, the differences are described only.

As will now be discussed in greater detail, in one preferredarrangement, the dispense interface 2000 illustrated in FIGS. 12 to 13comprises:

a. a part 2100 having multiple portions 2110, 2120, 2130, 2140, 2150,2160, 2170, 2180;

c. living hinges 2200, 2210, 2220, 2230, 2240, 2250, 2260;

d. a first piercing needle 240;

e. a second piercing needle 250;

f. an optional valve arrangement (not illustrated);

g. an injection needle 2600; and

h. axial attachment means 2700.

One exemplary difference between the dispense interface 200 and thedispense interface 2000 is the outer shape. Nevertheless, the dispenseinterface 2000 is attachable to a drug deliver device by axialattachment means 2700 as described above.

As illustrated in FIG. 12, neighbouring portions of the multipleportions 2110, 2120, 2130, 2140, 2150, 2160, 2170 and 2180 are connectedby respective living hinges 2200, 2210, 2220, 2230, 2240, 2250 and 2260.These multiple portions and living hinges are integrally formed from thesame polymer material by injection moulding. Therein, the living hingesmay be formed by pre-weakening the polymer material such thatneighbouring portions of the multiple portions can be folded along thepre-weakening towards each other as indicated by the arrows in FIG. 12.

For instance, portions 2130 and 2140 are connected by living hinge 2220.For instance, living hinge 2220 has a rotational axis A. Accordingly,the material may be pre-weakened along the rotational axis A such thatthe portions 2130 and 2140 can be folded along the rotational axis Atowards each other. For instance, the material is thinned along therotational axis A.

The multiple portions comprise body portions 2130, 2140 and 2160 andcover portions 2110, 2150 and 2180. The body portions 2130, 2140 and2160 comprise fluid grooves 2131, 2141 and 2161 arranged in theirfunctional surfaces 2132, 2142 and 2162.

As apparent from FIG. 13, the fluid grooves 2131, 2141 and 2161 aresealed by functional surfaces 2111, 2151 and 2181 of the cover portions2110, 2150 and 2180 facing the functional surfaces 2132, 2142 and 2162of the body portions 2130, 2140 and 2160 when the multiple portions arefolded towards each other. The multiple portions may be fixed by amaterial connection in this folded position. For instance, the multipleportions may be joined by laser welding at a mating/contact area.

In this folded position, the piercing needle 240 resides in fluidcommunication with the fluid groove 2131, and the piercing needle 250resides in fluid communication with the fluid groove 2161. The fluidgrooves 2131 and 2161 converge to the fluid groove 2141, to then providefor an output fluid path or the injection needle 2600.

Therein, the fluid groove 2141 resides in fluid communication with theinjection needle 2600. Injection needle 2600 may be a cannula likeneedle 406. Alternatively, the fluid groove 2141 may reside in fluidconnection with a fluid connector (e.g. a pierceable septum 270) suchthat needle assembly 400 or any other standard needle assembly may beattachable to the dispense interface 2000 (not illustrated).

Accordingly, dispense interface 2000 provides a fluid connection frompiercing needle 240 and 250 to a common outlet such as injection needle2600 when the multiple portions are folded towards each other.

The dispense interface 2000 may optionally comprise a valve arrangementsuch as one of the embodiments illustrated in FIGS. 14a to 14e . Thefunction of such an optional valve arrangement may basically relate tothe function of the first and second non return valve 262, 264 of thedispense interface 200. As described above, such a valve arrangement mayfor instance be constructed so as to prevent back flow and/or crosscontamination of the first and second medicaments 92, 102 contained inthe first and second reservoirs 90, 100, respectively. However, thedispense interface may also comprise no valve arrangement or a differentvalve arrangement.

As apparent from FIG. 13, the functional surfaces 2132, 2142 and 2162 ofthe body portions 2130, 2140 and 2160 are inclined to each other whenthe multiple portions are folded towards each other. The living hinge2220 connecting body portions 2130 and 2140 is for instance arrangedspaced from the functional surfaces 2132 and 2142 of the body portions2130 and 2140. In particular, the facing surfaces of body portions 2130and 2140 next to which the living hinge 2220 is arranged are inclinedsuch that the functional surfaces 2132 and 2142 draw an (obtuse) angle βwhen the multiple portions are folded towards each other.

FIGS. 14a to 14e illustrate embodiments of a valve arrangement for adispense interface such as the dispense interface 200 and 2000. In FIGS.14a to 14e the same reference signs are used for parts which aresimilar.

The valve arrangement may for instance be integrally formed with anotherpart of the dispense interface. Alternatively, the valve arrangement mayfor instance be manufactured separately from the other parts of thedispense interface.

For instance, the valve arrangement may be inserted (e.g.potted/over-moulded) into the multiple portions of the dispenseinterface 2000. For instance, the valve arrangement may at leastpartially be potted/over-moulded when the multiple portions areinjection moulded. For instance, the valve arrangement may at leastpartially be mounted in a separate step after the multiple portions havebeen injection moulded.

FIG. 14a illustrates a diaphragm/flap valve arrangement 3000 a. Thediaphragm/flap valve arrangement 3000 a has an inlet 3010 and an outlet3030. The inlet 3010 may for instance reside in fluid communication withone of the piercing needles 240, 250 of dispense interface 200 or 2000,and the outlet 3030 may for instance reside in fluid communication withholding chamber 280 of dispense interface 200 or injection needle 2600of dispense interface 2000.

The diaphragm/flap valve arrangement 3000 a has a flexiblediaphragm/flap 3040. When the fluidic pressure in the inlet 3010 isincreased (e.g. during a dose priming or a dose injecting step), thediaphragm/flap 3040 will change from an un-stressed state to a stressedstate. In the stressed state, the fluidic pressure bends thediaphragm/flap 3040 as indicated by the arrow in FIG. 14a so that thediaphragm/flap valve arrangement 3000 a opens. In this stressedcondition, the diaphragm/flap valve arrangement 3000 a will allow fluidto flow from the inlet 3010 to the outlet 3030. When the fluidicpressure in the inlet is removed, the diaphragm/flap 3040 will return toits initial position and seal the inlet 3010, preventing backflow.

FIG. 14b illustrates a shuttling valve arrangement 3000 b. The shuttlingvalve arrangement 3000 b has a tube 3050. The tube 3050 has two inlets3010, 3020 and an outlet 3030. The inlet 3020 may also reside in fluidcommunication with one of the piercing needles 240, 250 of dispenseinterface 200 or 2000. In the tube 3050 a movable element 3060 (e.g. apiston or a ball) is arranged.

The diameter of the movable element 3060 corresponds to the diameter ofthe tube 3050 such that the movable element 3060 is movable between afirst and a second (longitudinal) position in the tube 3050. In thefirst position (illustrated in FIG. 14b ), the movable element 3060seals the inlet 3010 and allows fluid to flow from the inlet 3020 to theoutlet 3030. In the second position (not illustrated), the movableelement 3060 seals the inlet 3020 and allows fluid to flow from theinlet 3010 to the outlet 3030. When the fluidic pressure in the inlet3010 is for instance increased (e.g. during a dose priming or a doseinjecting step), the movable element 3060 will be pushed towards thesecond position as indicated by the arrow in FIG. 14 b.

FIG. 14c illustrates a moulded duckbill valve arrangement 3000 c. Themoulded duckbill valve arrangement 3000 c has a first and a secondduckbill valve 3080, 3090. When the fluidic pressure in the inlet 3020is increased (e.g. during a dose priming or a dose injecting step), thesecond duckbill valve 3090 will change from an un-stressed state to astressed state. In the stressed state, the fluidic pressure inverts thenaturally flattened shape of the duckbill valve as indicated in FIG. 14cso that the duckbill valve opens. In this stressed condition, the secondduckbill valve 3090 will allow fluid to flow from the inlet 3020 to theoutlet 3030. When the fluidic pressure in the inlet 3020 is removed, thesecond duckbill valve 3090 will return to its flattened shape and sealthe inlet 3020, preventing backflow. The first duckbill valve 3080operates in a similar manner as the second duckbill valve 3090 when thefluidic pressure is increased in the inlet 3010.

FIG. 14d illustrates a flat spring valve arrangement 3000 d. The flatspring valve arrangement 3000 d has a first and a second flat spring3100, 3110. The first and the second flat spring 3100, 3110 may forinstance be integrally formed.

When the fluidic pressure in the inlet 3010 is increased (e.g. during adose priming or a dose injecting step), the first flat spring 3100 willchange from an un-stressed state to a stressed state. In the stressedstate, the fluidic pressure bends the first flat spring 3100 asindicated by the arrow in FIG. 14d so that the flat spring valvearrangement 3000 d opens. In this stressed condition, the flat springvalve arrangement 3000 d will allow fluid to flow from the inlet 3010 tothe outlet 3030. When the fluidic pressure in the inlet 3010 is removed,the first flat spring 3100 will return to its initial position and sealthe inlet 3010, preventing backflow. The second flat spring 3110operates in a similar manner as the first flat spring 3100 when thefluidic pressure is increased in the inlet 3020.

FIG. 14e illustrates a rotating flap valve arrangement 3000 e. Therotating flap valve arrangement 3000 e has a flap 3120 which isrotatably mounted in a valve chamber 3130. The valve chamber has twoinlets 3010, 3020 and an outlet 3030.

The flap 3120 is rotatable between a first and a second position. In thefirst position (illustrated in FIG. 14e ), the flap 3120 seals the inlet3010 and allows fluid to flow from the inlet 3020 to the outlet 3030. Inthe second position (not illustrated), the flap 3120 seals the inlet3020 and allows fluid to flow from the inlet 3010 to the outlet 3030.

When the fluidic pressure in the inlet 3010 is for instance increased(e.g. during a dose priming or a dose injecting step), the flap 3120will be pushed towards the second position as indicated by the arrow inFIG. 14 e.

The term “drug” or “medicament”, as used herein, means a pharmaceuticalformulation containing at least one pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a proteine, apolysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or afragment thereof, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exedin-3 or exedin-4 or an analogue or derivative ofexedin-3 or exedin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N—(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N—(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyhepta

decanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequence HHis-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;

or an Exendin-4 derivative of the sequence

H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(S1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exedin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Antibodies are globular plasma proteins (˜150 kDa) that are also knownas immunoglobulins which share a basic structure. As they have sugarchains added to amino acid residues, they are glycoproteins. The basicfunctional unit of each antibody is an immunoglobulin (Ig) monomer(containing only one Ig unit); secreted antibodies can also be dimericwith two Ig units as with IgA, tetrameric with four Ig units liketeleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

The Ig monomer is a “Y”-shaped molecule that consists of fourpolypeptide chains; two identical heavy chains and two identical lightchains connected by disulfide bonds between cysteine residues. Eachheavy chain is about 440 amino acids long; each light chain is about 220amino acids long. Heavy and light chains each contain intrachaindisulfide bonds which stabilize their folding. Each chain is composed ofstructural domains called Ig domains. These domains contain about 70-110amino acids and are classified into different categories (for example,variable or V, and constant or C) according to their size and function.They have a characteristic immunoglobulin fold in which two 0 sheetscreate a “sandwich” shape, held together by interactions betweenconserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ,and μ. The type of heavy chain present defines the isotype of antibody;these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies,respectively.

Distinct heavy chains differ in size and composition; α and γ containapproximately 450 amino acids and δ approximately 500 amino acids, whileμ and ε have approximately 550 amino acids. Each heavy chain has tworegions, the constant region (CH) and the variable region (VH). In onespecies, the constant region is essentially identical in all antibodiesof the same isotype, but differs in antibodies of different isotypes.Heavy chains γ, α and δ have a constant region composed of three tandemIg domains, and a hinge region for added flexibility; heavy chains μ andε have a constant region composed of four immunoglobulin domains. Thevariable region of the heavy chain differs in antibodies produced bydifferent B cells, but is the same for all antibodies produced by asingle B cell or B cell clone. The variable region of each heavy chainis approximately 110 amino acids long and is composed of a single Igdomain.

In mammals, there are two types of immunoglobulin light chain denoted byλ and κ. A light chain has two successive domains: one constant domain(CL) and one variable domain (VL). The approximate length of a lightchain is 211 to 217 amino acids. Each antibody contains two light chainsthat are always identical; only one type of light chain, κ or λ, ispresent per antibody in mammals.

Although the general structure of all antibodies is very similar, theunique property of a given antibody is determined by the variable (V)regions, as detailed above. More specifically, variable loops, threeeach the light (VL) and three on the heavy (VH) chain, are responsiblefor binding to the antigen, i.e. for its antigen specificity. Theseloops are referred to as the Complementarity Determining Regions (CDRs).Because CDRs from both VH and VL domains contribute to theantigen-binding site, it is the combination of the heavy and the lightchains, and not either alone, that determines the final antigenspecificity.

An “antibody fragment” contains at least one antigen binding fragment asdefined above, and exhibits essentially the same function andspecificity as the complete antibody of which the fragment is derivedfrom. Limited proteolytic digestion with papain cleaves the Ig prototypeinto three fragments. Two identical amino terminal fragments, eachcontaining one entire L chain and about half an H chain, are the antigenbinding fragments (Fab). The third fragment, similar in size butcontaining the carboxyl terminal half of both heavy chains with theirinterchain disulfide bond, is the crystalizable fragment (Fc). The Fccontains carbohydrates, complement-binding, and FcR-binding sites.Limited pepsin digestion yields a single F(ab′)2 fragment containingboth Fab pieces and the hinge region, including the H—H interchaindisulfide bond. F(ab′)2 is divalent for antigen binding. The disulfidebond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, thevariable regions of the heavy and light chains can be fused together toform a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1 C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

The invention claimed is:
 1. A dispense interface for an ejectiondevice, said dispense interface comprising: at least two inlets; atleast one outlet; and a part comprising multiple integral portions;wherein said multiple integral portions are connected by integral livinghinges such that said multiple integral portions are foldable towardseach other; wherein said multiple integral portions are configured toform a fluid channel arrangement between functional surfaces of saidmultiple integral portions facing each other when said multiple integralportions are folded towards each other; wherein said functional surfacesare outer surfaces of said multiple integral portions prior to saidmultiple integral portions being folded towards each other; wherein atleast two functional surfaces of said functional surfaces are inclinedto each other when said multiple integral portions are folded towardseach other into a folded position; and wherein said fluid channelarrangement comprises at least one fluid groove arranged on at least onefunctional surface of said functional surfaces so as to provide fluidcommunication between said at least two inlets and said at least oneoutlet when said multiple integral portions reside in the foldedposition.
 2. The dispense interface according to claim 1, wherein eachof said at least two inlets is formed from a fluid connector emptyinginto said fluid channel arrangement, and wherein each of said fluidconnectors is configured to establish a releasable fluid connection witha corresponding fluid connector of a fluid reservoir of said ejectiondevice when said dispense interface is attached to said ejection device.3. The dispense interface according to claim 1, wherein said at leastone outlet is formed from a fluid connector, wherein said fluid channelarrangement empties into said fluid connector, and wherein said fluidconnector is configured to establish a fluid connection with acorresponding fluid connector of a needle assembly, when said needleassembly is attached to said dispense interface.
 4. The dispenseinterface according to claim 1, wherein said at least one outlet isformed from a needle, and wherein said fluid channel arrangement emptiesinto said needle.
 5. The dispense interface according to claim 1, saiddispense interface further comprising: a valve arrangement configured tocontrol a fluid flow from said at least two inlets to said at least oneoutlet via said fluid channel arrangement.
 6. The dispense interfaceaccording to claim 1, wherein said multiple integral portions are foldedtowards each other, and wherein said multiple integral portions arefixed in the folded position by at least one of a mechanical connectionand a material connection.
 7. The dispense interface according to claim1, wherein said multiple integral portions comprise at least two bodyportions and at least two cover portions, and wherein each fluid channelof said fluid channel arrangement is formed between a functional surfaceof a respective body portion of said at least two body portions and afunctional surface of a respective cover portion of said at least twocover portions when said multiple integral portions are folded towardseach other.
 8. The dispense interface according to claim 7, wherein atleast one living hinge of said living hinges connecting two bodyportions of said at least two body portions is spaced from saidfunctional surfaces of the two body portions.
 9. The dispense interfaceaccording to claim 1, wherein said part having said multiple integralportions is integrally formed by an injection moulding.
 10. A method formanufacturing the dispense interface according to claim 1, said methodcomprising: moulding the part comprising multiple integral portions;folding said integral multiple portions towards each other; and fixingsaid integral multiple portions in the folded position.
 11. The methodaccording to claim 10, wherein fixing said multiple integral portions inthe folded position comprises at least one of: (i) gluing said multipleintegral portions to each other in the folded position, or (ii) weldingsaid multiple integral portions to each other in the folded position.12. A system, comprising the dispense interface according to claim 1;and the ejection device; wherein said dispense interface is attached tosaid ejection device.
 13. The system according to claim 12, said systemfurther comprising: a needle assembly; wherein said needle assembly isattached to said dispense interface.
 14. The system according to claim12, wherein said ejection device is a medical device configured to ejecta medicament.
 15. A method for using the system according to claim 12,said method comprising: attaching the dispense interface to the ejectiondevice, wherein the ejection device has at least two fluid reservoirs;ejecting a fluid from at least one of the reservoirs through saiddispense interface; and detaching said dispense interface from saidejection device.
 16. The dispense interface according to claim 1,wherein the at least two functional surfaces of said functional surfacesare inclined at an obtuse angle relative to each other when saidmultiple integral portions are in the folded position.
 17. The dispenseinterface according to claim 1, wherein said multiple integral portionscomprise more than two integral portions, and wherein the integralliving hinges comprise more than one integral living hinge.
 18. Thedispense interface according to claim 1, wherein the fluid channelarrangement is Y-shaped when the multiple integral portions are in thefolded position.
 19. The dispense interface according to claim 1,wherein said multiple integral portions comprise a body portion and acover portion, wherein the at least one fluid groove is on the outersurface of the body portion, and wherein the cover portion laterallyseals the at least one fluid groove on the body portion when the coverportion is folded toward the body portion to form the fluid channelarrangement between the cover portion and the body portion.
 20. Thedispense interface according to claim 19, wherein a ratio between alength of the fluid channel arrangement and a diameter of the fluidchannel arrangement is greater than a ratio of 20:1.